Preparation method of p-nitrophenylacetone

Abstract

The invention provides a preparation method of p-nitrophenylacetone, which comprises the following steps: S1, under the condition of participation of a nitrating agent and a dehydrating agent, completing nitration of phenylacetonitrile at 15-20 DEG C; S2, completing a hydrolysis process under the condition of 100-105 DEG C, separating out solids, conducting washing with water, and conducting recrystallization to obtain p-nitrophenylacetic acid crystals; S3, dissolving p-nitrophenylacetic acid crystals in an organic solvent, dropwise adding an acylating agent to complete an acylation process, and removing excessive acylating agent and solvent to obtain p-nitrophenylacetyl chloride; S4, adding the p-nitrophenylacetyl chloride into reaction liquid in batches at the temperature of 0 DEG C to complete the condensation process, so as to obtain diethyl 2-(4-nitrophenylacetyl)malonate, wherein the reaction liquid comprises a condensing agent, a catalyst and a water removal agent; and S5, removing free fatty acid on the diethyl 2-(4-nitrophenylacetyl)malonate under the condition of 120 to 125 DEG C to obtain p-nitrophenyl acetone. Cheap and easily available phenylacetonitrile is adopted as a starting raw material, so that a precursor chemical acetic anhydride is avoided, and industrial production is expected to be realized.

Description

technical field [0001] The present invention relates to a kind of preparation method of p-nitropropiophenone. Background technique [0002] Endometriosis is a common gynecological disease in women. The incidence rate of the disease reaches 10.0%, and there is an upward trend. It is mainly characterized by dysmenorrhea, pelvic pain and infertility. [0003] Relugolix is ​​a novel, non-peptide, orally available GnRH antagonist with the chemical name 1-(4-(1-(2,6-difluorobenzyl)-5-((dimethyl Amino)methyl)-3-(6-methoxypyridazin-3-yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-D]pyrimidine -6-yl)phenyl)-3-methoxyurea. It is a new drug jointly developed by Myovant and Takeda Pharmaceuticals for indications such as endometriosis and prostate cancer. The synthetic route of Relugolix is ​​as follows: figure 1 shown. [0004] The compound p-nitropropiophenone is the starting material for the preparation of relugoli, and currently no domestic manufacturers have achieved large-scale ...

AI Technical Summary

Problems solved by technology

[0006] Although the above synthesis method is short, the raw material acetic anhydride belongs to the second category of precursor chemicals supervised by the state, and the purchase and storage procedures are cumbersome

And inevitably can produce by-product 1,3-bis-(4-nitrophenyl) acetone ( image 3 is the structural formula), the by-product impurities are difficult to remove, which seriously affects the quality of the product

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